S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon

Chronic ethanol consumption by baboons (50% of energy from a liquid diet) for 18 to 36 mo resulted in significant depletion of hepatic S-adenosyl-L-methionine concentration: 74.6 +/- 2.4 nmol/gm vs. 108.9 +/- 8.2 nmol/gm liver in controls (p less than 0.005). The depletion was corrected with S-adenosyl-L-methionine (0.4 mg/kcal) administration (102.1 +/- 15.4 nmol/gm after S-adenosyl-L-methionine-ethanol, with 121.4 +/- 11.9 nmol/gm in controls). Ethanol also induced a depletion of glutathione (2.63 +/- 0.13 mumol/gm after ethanol vs. 4.87 +/- 0.36 mumol/gm in controls) that was attenuated by S-adenosyl-L-methionine (3.89 +/- 0.51 mumol/gm in S-adenosyl-L-methionine-methanol vs. 5.22 +/- 0.53 mumol/gm in S-adenosyl-L-methionine controls). There was a significant correlation between hepatic S-adenosyl-L-methionine and glutathione level (r = 0.497; p less than 0.01). After the baboons received ethanol, we observed the expected increase in circulating levels of the mitochondrial enzyme glutamic dehydrogenase: 95.1 +/- 21.4 IU/L vs. 13.4 +/- 1.8 IU/L; p less than 0.001, whereas in a corresponding group of animals given S-adenosyl-L-methionine with ethanol, the values were only 30.3 +/- 7.1 IU/L (vs. 9.6 +/- 0.7 IU/L in the S-adenosyl-L-methionine controls). This attenuation by S-adenosyl-L-methionine of the ethanol-induced increase in plasma glutamic dehydrogenase (p less than 0.005) was associated with a decrease in the number of giant mitochondria (assessed in percutaneous liver biopsy specimens), with a corresponding change in the activity of succinate dehydrogenase, a mitochondrial marker enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma apolipoproteins in patients with multi-infarct dementia

We examined 27 elderly patients with multi-infarct dementia developed on the basis of cerebral arteriosclerosis. The levels of plasma cholesterol and triglyceride in the patients were 177 +/- 48 and 91 +/- 27 mg/dl (mean +/- SD), respectively. Despite normal plasma lipid levels, the patients had significantly higher plasma apo B (102 +/- 30 vs. 82 +/- 21 mg/dl for controls, P less than 0.01) and lower plasma apo A-I levels (104 +/- 25 vs. 130 +/- 22 mg/dl for controls, P less than 0.01) than the controls. Isoelectric focusing of apo E showed a 2-fold higher relative frequency for the epsilon 4 allele in patients than in Japanese controls (20.8 vs. 8.6-11.7% of total, P less than 0.05). The patients with phenotypes of E4/4 (n = 1) and E4/3 (n = 8) had higher plasma cholesterol levels than those with E3/3 (n = 15) (196 +/- 45 vs. 169 +/- 43 mg/dl). The results indicate that the patients had abnormalities in plasma lipoprotein metabolism and this may contribute to the development of cerebral arteriosclerosis.     

Insulin and C-peptide plasma levels in patients with severe chronic pancreatitis and fasting normoglycemia

The aim of the present study was to evaluate insulin secretion by the pancreatic B cell in a group of patients with severe chronic pancreatitis and without overt diabetes. For this purpose we have measured plasma insulin and C-peptide peripheral levels in the fasting state and after a 100-g oral glucose load in 10 patients with severe chronic pancreatitis and fasting normoglycemia, and in 10 sex-, age-, and weight-matched healthy controls. As compared to normal subjects, patients with chronic pancreatitis showed: (1) significantly higher plasma glucose levels after oral glucose load (area under the plasma glucose curve 1708 +/- 142 vs 1208 +/- 47 mmol/liter X 240 min, P less than 0.005); (2) plasma insulin levels significantly higher at fasting (0.11 +/- 0.008 vs 0.08 +/- 0.005 nmol/liter, P less than 0.01) but not after oral glucose administration (area under the plasma insulin curve 79 +/- 12 vs 88 +/- 16 nmol/liter X 240 min); (3) significantly lower plasma C-peptide concentrations both in the fasting state (0.15 +/- 0.01 vs 0.54 +/- 0.05 nmol/liter, P less than 0.001) and after oral glucose load (area under the plasma C-peptide curve 211 +/- 30 vs 325 +/- 37 nmol/liter X 240 min, P less than 0.05). The finding of diminished plasma C-peptide levels suggests that chronic pancreatitis is associated with an impaired B-cell function even in the absence of overt diabetes. The increased or unchanged plasma insulin levels in spite of decreased plasma C-peptide concentrations indicate that in chronic pancreatitis insulin metabolism is reduced, most likely within the liver.     

Levels of acylation stimulating protein in obese women before and after moderate weight loss

Acylation stimulating protein (ASP) is a small (MW 14,000) basic (pI 9.0) protein which has only recently been purified from human plasma. Since ASP is the most potent known stimulant of triglyceride synthesis in human adipose tissue, the present study was designed to determine if plasma ASP was elevated in patients with moderate obesity, and if so, whether this level changed with weight loss. Fasting plasma ASP levels were determined by competitive ELISA immunoassay in 10 obese women before weight loss, immediately after weight loss, and 3 months after maintaining weight reduction. Their plasma ASP results were compared to 17 age and sex-matched lean controls. With weight loss, plasma ASP decreased significantly: 19.6 +/- 10.7 mg/dl before weight loss vs 15.0 +/- 9.5 mg/dl after weight loss vs 13.8 +/- 7.7 mg/dl 3 months after being weight stable, P less than 0.05 initial vs final value. Nevertheless, plasma ASP was significantly higher than the control value at all three times. Thus, before weight loss, the average ASP in the obese group was four times that in the control group (19.6 +/- 10.7 vs 5.1 +/- 3.6 mg/dl, P less than 0.0005) while even 3 months after weight loss, it remained almost three times above the control group (13.8 +/- 7.7 vs 5.1 +/- 3.6 mg/dl, P less than 0.0005). The data suggest, therefore, that an elevated plasma level of ASP is common in obesity, that the level of plasma ASP may reflect the fat cell mass present in an individual, and raises the possibilities that ASP may play a role in initiation or maintenance of the obese state.     

Increased peripheral circulating inflammatory cells and plasma inflammatory markers in patients with variant angina

BACKGROUND: Emerging data suggest that inflammation may play an important role in the pathogenesis of coronary artery disease. However, the relation of inflammatory status to coronary vasospasm has been less investigated in patients with variant angina (VA). PURPOSE: The aim of this study, therefore, was to determine peripheral circulating white blood cells as well as monocyte cells and plasma C-reactive protein (CRP) and interleukin-6 (IL-6) levels in patients with VA, and to compare patients with VA, stable coronary artery disease, and controls with angiographically normal coronary arteries. METHOD: Thirty-three consecutive patients with documented VA, 26 with stable coronary artery disease, and 22 normal controls (with angiographically normal coronary arteries) were involved in this study. The peripheral blood was taken, and white blood cells and monocyte cells were counted. The plasma concentrations of CRP and IL-6 were also evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: The data showed that white blood cell counts and monocyte cell counts were significantly higher in patients of the VA group than in the other two groups (white blood cell counts: 7340+/-1893/mm vs. 6187+/-1748/mm vs. 5244+/-1532/mm, P<0.05, respectively; monocyte cell counts: 510+/-213/mm vs. 425+/-209/mm vs. 383+/-192/mm, P<0.05, respectively). Similarly, levels of plasma CRP and IL-6 were also significantly higher in patients of the VA group than in patients with stable coronary artery disease (CRP: 0.42+/-0.21 mg/l vs. 0.27+/-0.14 mg/l; IL-6: 10.4+/-1.0 pg/dl vs. 6.2+/-0.7 pg/dl, P<0.01, respectively), and patients with normal controls (CRP: 0.42+/-0.21 mg/l vs. 0.17+/-0.10 mg/l; IL-6: 10.4+/-1.0 pd/dl vs. 3.0+/-0.7 pg/dl, P<0.01, respectively). The multivariate analysis showed that CRP was the independent variable most strongly associated with VA. CONCLUSION: Taken together, these findings suggested that more chronic, severe inflammation might be involved in the pathogenesis of VA, manifested by increased counts of circulating inflammatory cells and elevated plasma levels of CRP and IL-6.     

Changes in nephrogenous cyclic AMP excretion and plasma cyclic AMP following treatment of hyperthyroidism

Plasma cyclic AMP (PcAMP) concentration and the excretion of cyclic AMP/dl GF were estimated in 11 thyrotoxic patients before and after medical treatment. PcAMP concentrations were significantly higher during hyperthyroidism (2.30 +/- 0.69 vs 1.88 +/- 0.71 nmol/dl; P less than 0.05), and total urinary cyclic AMP (TcAMP) excretion showed no significant changes (3.24 +/- 0.64 vs 3.44 +/- 1.77 nmol/dl GF). Nephrogenous (NcAMP) excretion rose significantly (1.00 +/- 0.82 vs 1.68 +/- 1.31 mmol/dl GF; P less than 0.025). The increase in NcAMP excretion correlated significantly with the decrease in serum T3 levels (r = -0.46; P less than 0.05). Serum iPTH levels showed no significant change. Both the serum Ca, corrected for serum total protein and TmPO4/GFR declined after treatment (respectively 2.44 +/- 0.13 vs 2.33 +/- 0.08 mmol/l; P less than 0.05 and 1.18 +/- 0.29 vs 1.05 +/- 0.22 mmol/l; P less than 0.05). It is concluded that the rise in NcAMP excretion corroborates the concept of increasing parathyroid activity following the treatment of hyperthyroidism.     

Concentration Dependency of Ethanol Elimination Rates in Baboons: Effect of Chronic Alcohol Consumption

Ethanol elimination rates were measured in 7 baboons fed alcohol for 2--7 yr (and their controls) by using a constant ethanol infusion to maintain blood ethanol at three different levels; 5, 10, and 50 mM. Ethanol elimination rates were significantly faster at a blood ethanol level of 50 mM than at 10 or 5 mM in both alcohol-fed and control animals. The difference between 50 mM and 5 mM concentration was 36% in alcohol-fed and 25% in control animals. In baboons fed ethanol chronically, the ethanol elimination rates were significantly faster than in pair-fed controls at 50 mM (179 +/- 10.0 mg/kg/hr versus 144 +/- 9.8) and at 10 mM (148 +/- 4.1 versus 114 +/- 8.2), but not at 5 mM. Even if one takes into account the extrahepatic losses, these differences cannot be explained solely by the elimination of ethanol through the low Km alcohol dehydrogenase pathway, and these observations indicate that a non-ADH system significantly contributes to ethanol elimination in vivo, especially in alcohol-fed baboons.     

Characterization of low-density lipoproteins from patients with recessive X-linked ichthyosis

We investigated lipoprotein metabolism in 14 patients with recessive X-linked ichthyosis (RXLI), a metabolic disease characterized by scaly skin, corneal opacity and steroid sulfatase deficiency. Plasma total cholesterol (TC) levels ranged from normal to slightly low (mean +/- SD: 156 +/- 28 mg/dl). Four patients showed a mild or moderate elevation of plasma triglyceride (TG) levels ranging from 150 to 365 mg/dl. The apoprotein B (apo B) to TC ratio was higher than in normal controls (0.63 +/- 0.11 vs. 0.52 +/- 0.07, P less than 0.01), while plasma apoB levels were within the normal range (99 +/- 17 mg/dl). Polyacrylamide gel electrophoretic mobility of low-density lipoprotein (LDL) was markedly increased in all patients, and further analyses showed that this finding was not due to a change in the particle size of the LDL but to an increased content of cholesterol sulfate (1.0-2.3% of the LDL-cholesterol content). In addition to the alteration of electrophoretic mobility, marked changes in the lipid and apoprotein compositions of the LDL fraction were observed; cholesterol ester content in LDL (LDL-CE) was significantly lower than that of control subjects (37 +/- 4% vs. 41 +/- 2% of total lipids, P less than 0.01), while the triglyceride content (LDL-TG) and apo B to cholesterol ratios in LDL were significantly higher than those of controls (18 +/- 7 vs. 10 +/- 2, P less than 0.001; 1.21 +/- 0.19 vs. 0.73 +/- 0.05, P less than 0.001, respectively). This anionized LDL, in which cholesterol sulfate was increased, was shown to bind to the LDL receptor of fibroblasts to much the same extent as normal LDL. In conclusion, the increase in cholesterol sulfate in LDL fraction not only alters the electrophoretic moiety but also the relative contents of apoB, cholesterol, and triglyceride in the lipoprotein. It does not change the affinity of LDL for the LDL receptor.     

Arterial lipid biochemistry in the spontaneously hyperlipidemic Zucker rat and its similarity to early atherogenesis

In the present studies, arterial lipid metabolism was evaluated in the spontaneously hyperlipidemic obese Zucker rat (fa/fa), the lean Zucker rat (Fa/-), and the Sprague-Dawley (SD) rat. Mean serum cholesterol levels in the obese Zucker, lean Zucker and SD rats were 216 +/- 18 mg/dl, 145 +/- 14 mg/dl and 84 +/- 5 mg/dl, respectively. Arterial cholesterol content was in the same rank order as plasma cholesterol and ranged from a mean of 2.23 +/- 0.10 mg/gm wet wt. in the obese rats to 1.36 +/- 0.04 mg/gm wet wt. in the SD rats. The increased arterial sterol in the obese rats was associated with increased lipid metabolism activity. The in vitro incorporation of [14C]oleate into arterial cholesteryl esters was increased 3-4-fold (P less than 0.01) and incorporation into phospholipids and triglycerides was also elevated (P less than 0.001 and P less than 0.01, respectively). The arterial sterol content and arterial lipid metabolism pattern observed in obese Zucker rat aortas are similar to those found in vessels of other species undergoing atherogenic change.     

PLASMA CONCENTRATIONS OF SEX HORMONES IN POSTMENOPAUSAL WOMEN IN NON-ALCOHOLIC CIRRHOSIS

Sex hormone and sex hormone binding globulin (SHBG) levels were measured in the plasma of postmenopausal women with non-alcoholic liver cirrhosis (n = 24) and compared with levels in matched controls (n = 21). Plasma oestradiol was elevated: 80 vs 30 pmol/l, P less than 0.005 (median values). Plasma SHBG was elevated, 15 vs 10 mg/dl, P less than 0.001. Plasma dehydroepiandrosterone sulphate levels were low, 0.35 vs 2.0 mumol/l, P less than 0.0005, as were plasma androstenedione levels, 2.5 vs 4.5 nmol/l, P less than 0.05. There was no significant difference in plasma testosterone. These data suggest that liver disease per se alters sex hormone and sex hormone binding globulin levels in postmenopausal women.     

Effect of lovastatin on hemorheology in type II hyperlipoproteinemia

To assess the effect of lovastatin on blood rheology, the hemorheological determinants fibrinogen, red cell aggregation, plasma viscosity, hematocrit and platelet aggregation (spontaneous and ADP-induced) were studied in 15 patients with type II hyperlipoproteinemia in the course of treatment with lovastatin. Prior to therapy, fibrinogen (Fgen), red cell aggregation (RCA-S, RCA-L) and plasma viscosity (PV) as well as cholesterol (Chol) and triglycerides (Tg) were increased in the hyperlipemic patients compared with healthy normolipemic controls (Fgen: 319.3 +/- 65 vs. 269.8 +/- 48 mg/dl; RCA-S: 7.93 +/- 1 vs. 6.62 +/- 1, RCA-L: 9.86 +/- 1 vs. 7.8 +/- 1 arbitrary units; PV: 1.75 vs. 1.63 mPa/s; Chol: 317.0 +/- 32 vs. 176.5 +/- 21 mg/dl; Tg: 154.5 +/- 88 vs. 72.8 +/- 16 mg/dl; all P less than 0.05). Three months of treatment with lovastatin resulted in a marked decrease in red cell aggregation and plasma viscosity, parallel to a fall in cholesterol (the following pretreatment values were monitored after a standard lipid-lowering diet; RCA-S: 7.59 +/- 1 vs. 6.65 +/- 0.9, RCA-L: 9.34 +/- 1 vs. 8.15 +/- 1 arbitrary units; PV: 1.74 vs. 1.65 mPa/s; Chol: 309.8 +/- 41 vs. 217.1 +/- 30 mg/dl; all P less than 0.01); fibrinogen however, remained unchanged throughout the treatment period (346.4 +/- 73.3 vs. 330.5 +/- 70.2 mg/dl, n.s.). No differences were seen in hematocrit and platelet aggregability between hyperlipemic patients and controls and no changes occurred in these parameters during the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of weight loss and weight maintenance on the serum lipids, lipoprotein lipase and hepatic triglyceride lipase activities in obese rats

The effects of obesity, weight loss and weight maintenance on the serum lipid levels and lipoprotein lipase and hepatic triglyceride lipase were investigated in rats. Obesity induced by high-fat (HF) feeding was associated with decreased serum triglyceride levels (HF: 70.3 +/- 8.2, control (CON): 140.0 +/- 26.9 mg/dl, P less than 0.05), increased lipoprotein lipase (LPL, HF: 593.2 +/- 10.6 vs CON: 280 +/- 19.5 nmol FFA/min per mg tissue, P less than 0.05) and suppressed hepatic triglyceride lipase activities (HTGL, HF: 14.2 +/- 0.5 vs CON: 18.0 +/- 0.4 nmol FFA/min per mg tissue, P less than 0.01). After a weight loss to the level of control rats, weight maintenance was achieved either by high-protein (HP) or chow feedings (CH). Both high-protein (HFHP) and chow (HFHC) groups had similar weights but only high-protein feeding restored the normal body compositions. Both groups of rats had higher total (TC, HFHP: 146 +/- 10.7; HFCH: 104.8 +/- 5.1 mg/dl), and high density lipoprotein cholesterol levels (HDL-C, HFHP: 100.8 +/- 15.6; HFCH: 75.5 +/- 5.5 mg/dl) and lower lipoprotein lipase (HFHP: 238.2 +/- 15.8, HFCH: 354.8 +/- 34.9 nmol FFA/min per mg tissue) and hepatic triglyceride activities (HFHP: 16.3 +/- 1.1; HFCH: 14.5 +/- 0.6 nmol FFA/min per mg tissue) than control rats (TC: 70.1 +/- 4.7 mg/dl; HDL-C: 14.2 +/- 4.3 mg/dl; LPL: 742.4 +/- 82.3 nmol FFA/min per mg tissue; HTGL: 20.5 +/- 1.0 nmol FFA/min per mg tissue, P less than 0.05 to 0.005) or the rats who regained weight by resuming high-fat feeding (TC: 59.5 +/- 6.7 mg/dl; HDL-C: 10.2 +/- 6.7 mg/dl; LPL: 1284.3 +/- 90 nmol FFA/min per mg tissue; HTGL: 22.2 +/- 1.9 nmol FFA/min per mg tissue, P less than 0.05 to 0.005). The high protein-group had significantly higher total and high-density-lipoprotein cholesterol levels than the chow fed animals despite comparable body weights in both groups. The findings of this study suggest that weight maintenance induced by high protein feeding is more successful in restoring the normal body composition. However, high protein feeding is also associated with high serum cholesterol levels. The clinical applications of these findings need to be evaluated further.     

Evidence suggesting that the sympathetic nervous system mediates thyroidal depression in turpentine-induced nonthyroidal illness syndrome

Acute superior cervical ganglionectomy (SCGx) induces in the rat a supraliminal release of neurotransmitter in the innervated tissues (i.e., thyroid gland). This temporary adrenergic hyperactivity is correlated with a significant depression of the thyroid economy resembling the nonthyroidal illness (NTI) syndrome in the rat, and suggest that the sympathetic nervous system may mediate thyroidal changes in NTI. In order to gain further insight into the thyroidal depression in the NTI syndrome, we studied the thyroidal norepinephrine (NE) turnover in turpentine oil (TURP)-induced NTI syndrome and the role of the cervical ganglia (SCG) in the development of NTI in the rat. TURP administration to sham operated rats induced a rapid and significant fall in plasma T4 and TSH levels, in the thyroidal response to exogenous TSH (TIU) and in the thyroidal NE content compared to controls (sham + saline) (T4: 3.1 +/- 0.3 vs. 5.1 +/- 0.6 micrograms/dl, respectively, mean +/- SE, p less than 0.02; TSH: 1.4 +/- 0.4 vs. 4.7 +/- 1.4 ng/ml, respectively, p less than 0.05; TIU: 92 +/- 14 vs. 201 +/- 20 cpm.microliter thyroid/cpm.mg plasma (T/P ratio), respectively, p less than 0.01; thyroidal NE: 680 +/- 20 vs. 761 +/- 29 pg/mg thyroid, respectively, p less than 0.05). The thyroidal turnover rate of NE, however, was significantly increased in TURP-injected rats compared to controls (122 +/- 13 vs. 86 +/- 10 pg/mg/h, respectively, p less than 0.05). TURP injection to chronic SCGx rats induced a similar fall in plasma TSH compared to controls (SCGx + saline) (1.3 +/- 0.2 vs. 4.3 +/- 1.1 ng/ml, respectively, p less than 0.02); plasma T4 and TIU, however, did not change significantly (T4: 3.4 +/- 0.4 vs. 3.7 +/- 0.3 micrograms/dl, respectively, NS; TIU: 172 +/- 8 vs. 226 +/- 27 T/P ratio, respectively, NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of HDL and lipoproteins intermediate to LDL and HDL in the serum of pedigreed baboons fed an atherogenic diet

A lipoprotein species with ultracentrifugal flotation rates (F0(1.20) 9-28) intermediate to high density lipoproteins (HDL, F0(1.20) 0-9) and low density lipoproteins (LDL, F0(1.20) 28-56) found in the plasma of certain pedigreed baboons fed an atherogenic diet was studied by gradient gel electrophoresis (GGE) and ultracentrifugal techniques. These lipoproteins were found to be heterogeneous in size (125-220 A) and hydrated density (1.028-1.080 g/ml). The major apolipoprotein in all density subfractions of the F0(1.20) 9-28 lipoproteins exhibited the molecular weight (2.8 X 10(4) daltons) and immunochemical properties of apolipoprotein A-I (apoA-I). Protein corresponding to apolipoprotein E (apoE, 3.5 X 10(4) daltons) was observed primarily in the less dense subspecies of F0(1.20) 9-28 lipoproteins. Some low molecular weight (1.8 X 10(4), 1.3 X 10(4), and 1.1 X 10(4) daltons) apolipoproteins were also detected. At low serum F0(1.20) 9-28 lipoprotein concentrations, only the smaller, more dense, protein-rich species were present; at higher F0(1.20) 9-28 concentrations, the larger, less dense species were observed in addition to the small species. The HDL of pedigreed baboons in families with and without serum F0(1.20) 9-28 lipoproteins were also characterized. The HDL of both groups of progeny consisted of a similar set of 5 subpopulations designated HDL-I through HDL-V determined by GGE. HDL-I, consisting of material 100-125 A in size, was the major HDL subpopulation. ApoA-I was the major protein moiety in all HDL subpopulations; none contained apoE. Baboons in families with F0(1.20) 9-28 lipoproteins had more HLD-I (292 +/- 80 mg/dl vs. 235 +/- 55 mg/dl) and less HDL-II (86 +/- 22 mg/dl vs. 135 +/- 34 mg/dl) than baboons in families without F0(1.20) 9-28 lipoproteins; both groups showed identical total HDL concentrations (446 +/- 90 mg/dl and 444 +/- 49 mg/dl, respectively). Among those baboons in families with F0(1.20) 9-28 lipoproteins, there was an inverse correlation between F0(1.20) 9-28 concentration and total HDL, HDL-I and HDL-II concentrations, indicating a possible metabolic relationship between these HDL subpopulations and the F0(1.20) 9-28 species.     

Beneficial effect of fibronectin administration on chronic nephritis in rats

We studied the effect of fibronectin (FN) on the course of chronic nephritis (induced by daily injections of ovalbumin) and on the clearance and catabolism of immune complexes in Wistar rats. Rats with chronic nephritis were treated with FN (2.5 mg/kg/48 hours) for 15 days after proteinuria was first detected. In rats with untreated nephritis, urinary protein levels increased from 40 +/- 22 mg/day (mean +/- SD) to 339 +/- 68 mg/day during the 15 days of the study (P less than 0.0005). This statistically significant increase was not observed in rats treated with FN (mean +/- SD 58 +/- 46 mg/day to 124 +/- 112 mg/day). Rats treated with FN showed a higher total serum protein level than did the untreated animals (mean +/- SD 6.4 +/- 0.3 gm/dl versus 5.1 +/- 0.5 gm/dl; P less than 0.0125), as well as a significant reduction in mesangial and glomerular basement membrane deposits. Untreated nephritic rats demonstrated delayed plasma clearance of 125I-labeled aggregated IgG (plasma half-life [T1/2] 3.03 +/- 0.6 minutes) and less catabolism of these aggregates at 30 minutes (mean +/- SD 15 +/- 1.7%) than did the normal rats (T1/2 1.5 +/- 0.2 minutes, 22 +/- 2.8%, respectively; P less than 0.0005). Both parameters were within normal limits in the FN-treated rats (T1/2 1.6 +/- 0.4 minutes, 22 +/- 6%, respectively). In vitro, FN induced a significant increase in aggregated IgG catabolism by Kupffer cells and peritoneal macrophages from normal rats. These results show that FN reduces the proteinuria and histologic lesions of chronic nephritis in rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

High concentrations of Lp(a) lipoprotein in serum are common among patients with abdominal aortic aneurysms

The serum concentrations of Lp(a) lipoprotein was determined in 57 patients with abdominal aortic aneurysms (AAAs) and in 56 controls. Twentynine of the AAA-patients also suffered from other cardiovascular diseases and eleven had brothers and sisters with AAAs. Lp(a) was significantly higher among the AAA-patients than among the controls (22.3 +/- 24.3 vs 12.6 +/- 20.4 mg/dl, p less than 0.01). The 28 AAA-patients without other cardiovascular diseases had a somewhat higher Lp(a) in serum than the other AAA-patients, but this difference was not statistically significant (26.4 +/- 28.4 vs 18.5 +/- 19.3 mg/dl). The 11 AAA-patients with AAAs in the family didn't differ from the other AAA-patients concerning Lp(a) in serum. Several genetic markers were also studied, and the seven Kell-positive AAA-patients had a significantly lower Lp(a) in serum than the 47 Kell-negative AAA-patients (7.0 +/- 10.3 vs 25.7 +/- 25.2 mg/dl, p less than 0.05).     

Effect of alcohol intake and exercise on plasma high-density lipoprotein cholesterol subfractions and apolipoprotein A-I in women

Abstinence from alcohol consumption for 3 weeks was followed by 3 weeks of wine intake in 18 inactive and 18 physically active premenopausal women (runners). The runners weighed less and had higher plasma high-density lipoprotein (HDL) cholesterol and lower low-density lipoprotein cholesterol levels than the inactive women. There were no differences between groups in plasma total cholesterol, triglyceride and apolipoprotein A-I concentrations. Runners had higher plasma HDL2 cholesterol concentrations than inactive women (34 +/- 17 vs 19 +/- 12 mg/dl), but HDL3 cholesterol concentration did not differ between the groups (41 +/- 10 vs 39 +/- 9 mg/dl). Addition of 35 g/day of ethanol for 3 weeks did not result in a significant change in either group for any of the variables measured. The amount of exercise appears to be a more important determinant of plasma lipoproteins and apolipoprotein A-I than alcohol intake in premenopausal women.     

Low testosterone levels in diabetic men and animals: a possible role in testicular impotence

Poorly controlled NOD spontaneously diabetic mice were proven to have significantly less plasma and testicular testosterone than well-controlled diabetic mice (489 +/- 15 ng/dl and 3.89 +/- 0.79 micrograms/100 g tissue, vs. 176 +/- 24 and 9.00 +/- 1.24, respectively), and these in turn had significantly less than NOD non-diabetic control mice. These data were consistent with our previous observation of a decrease in total plasma and testicular testosterone levels in streptozotocin diabetic rats. A greater difference between total plasma testosterone levels and free testosterone levels was found in streptozotocin diabetic rats (17 +/- 4 ng/dl vs. 91 +/- 7 ng/dl) than in control rats (660 +/- 141 vs. 352 +/- 77). Fat droplets, depicting blocked testosterone synthesis, were found in the testicular Leydig cells of streptozotocin diabetic rats and disappeared with insulin treatment. No difference was found among plasma total testosterone concentrations in people in different stages of diabetes, as had been previously reported. However, human diabetic males, free of complications but poorly controlled, had less free testosterone than those without complications but well controlled (18.0 +/- 2.0 pg/ml vs. 22.8 +/- 1.3), who in turn had significantly less than age-matched controls (25.3 +/- 1.1 pg/ml). These data suggest gonadal dysfunction in diabetes mellitus.     

Decreased hepatic glycogen content and accelerated response to starvation in rats with carbon tetrachloride-induced cirrhosis

Glucose homeostasis and fatty acid metabolism are abnormal in patients with cirrhosis. To assess the metabolic response to starvation in an animal model of cirrhosis, glycogen and fuel metabolism were characterized in rats with CCl4-induced cirrhosis studied 2 wk after 10 weekly doses of CCl4. Plasma concentrations of glucose and beta-hydroxybutyrate were not different between fed CCl4-treated and control rats, but plasma nonesterified fatty acid concentrations were higher in cirrhotic animals (0.25 +/- 0.01 vs. 0.39 +/- 0.04 mmol/L; p less than 0.05). After 12 hr of starvation, the plasma nonesterified fatty acid concentration had reached 0.58 +/- 0.04 mmol/L in CCl4-treated rats, compared with 0.38 +/- 0.04 mmol/L in control rats (p less than 0.05). The redistribution of the hepatic carnitine pool toward acylcarnitines, which is characteristic of starvation, was complete after fasting for 12 hr in the CCl4-treated rats, compared with the 24 hr required in control rats. In fed cirrhotic rats, liver glycogen content per gram liver was decreased by 64% compared with control rats (30.0 +/- 5.1 vs. 10.8 +/- 1.1 mg/gm liver wet wt; p less than 0.05). After 12-hr fasting, hepatic glycogen content had fallen to 14.3 +/- 3.9 and 4.8 +/- 0.4 mg/gm liver wet wt (p less than 0.05) in control and cirrhotic animals, respectively. To further characterize the status of glycogen metabolism in cirrhotic livers, activities of glycogen synthase and glycogen phosphorylase were determined. Hepatic active and total glycogen phosphorylase activities normalized to hepatocellular content were unaffected by CCl4 treatment, whereas total glycogen synthase activity was increased by 45%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Systemic and renal vascular responses to dietary calcium and vitamin D

To assess the consequences of hypercalcemia on systemic and renal hemodynamics, vasoactive hormones, and water and electrolyte excretion in intact, conscious mongrel dogs, measurements in 10 dogs receiving 100 mg/kg calcium gluconate and 10,000 U/kg vitamin D daily for 2 weeks were compared with measurements made in 10 time-control dogs not receiving calcium or vitamin D. Hypercalcemia induced by dietary supplementation with calcium and vitamin D resulted in profoundly reduced glomerular filtration rate (40 vs 78 ml/min in controls; p less than 0.005), estimated renal plasma flow (145 vs 267 ml/min in controls; p less than 0.005), and renal blood flow (254 vs 441 ml/min in controls; p less than 0.005). Renal resistance was significantly increased in the hypercalcemic dogs (0.57 +/- 0.07 vs 0.28 +/- 0.01 mm Hg/ml/min; p less than 0.005). Hypercalcemia also resulted in increased fractional excretion of water (4.8 vs 1.4% in controls; p less than 0.005), sodium (1.4 vs 0.6% in controls; p less than 0.005), calcium (1.7 vs 0.7% in controls; p less than 0.01), and magnesium (10.2 vs 4.1% in controls; p less than 0.005). Systolic blood pressure (160 vs 172 mm Hg in controls; p less than 0.05) and stroke volume were lower (0.024 vs 0.036 L/beat in controls; p less than 0.005) in hypercalcemic dogs, presumably because of the diuresis, while total peripheral resistance was higher (36 vs 31 mm Hg/L/min; p less than 0.05) in controls. Magnesium levels were significantly lower in the experimental group (1.3 vs 1.7 mg/dl in controls; p less than 0.0005). Aldosterone levels, plasma renin activity, and urinary prostaglandin excretion were not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)